Dissertations / Theses: 'Biophysical modelling'

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Lorz, Alexander Stephan Richard. "Partial differential equations modelling biophysical phenomena." Thesis, University of Cambridge, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.609381.

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CARANTE, MARIO PIETRO. "Biophysical modelling for cancer ion therapy." Doctoral thesis, Università degli studi di Pavia, 2017. http://hdl.handle.net/11571/1203385.

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Padarian, Campusano José Sergei. "Provision of soil information for biophysical modelling." Thesis, The University of Sydney, 2014. http://hdl.handle.net/2123/12278.

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This thesis is concerned with the generation of a framework for addressing soil data needs, specifically for biophysical modelling. The soil system is an important ecosystem actor, supporting most of the worlds' food production and being the major terrestrial carbon stocks, thereby information about it is crucial for management and policy making. To provide this information, it is important to deliver information of the highest possible quality; thus the need to define guidelines to standardise, not only the methodologies, but the minimum requirements that information must meet. In this project, providing soil data is addressed in two ways. The first scenario investigates the use of soil information to predict other soil properties, using pedotransfer function (PTFs). In the second scenario, it is assumed that the end-user does not have extra information about the soil properties at a specific location. In this case, the use of existing soil maps is a traditional solution, thus a framework for generating maps at national/continental scale, using digital soil mapping (DSM) techniques, is proposed.

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Dale, Michael Anthony Joseph. "Global Energy Modelling : A Biophysical Approach (GEMBA)." Thesis, University of Canterbury. Mechanical Engineering, 2010. http://hdl.handle.net/10092/5156.

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The aim of this thesis is to take a broad conceptual overview of the global energy system and investigate what the aims of sustainability might entail for such a system. The work presented uses a biophysical economic approach in that the dynamics of the global economy are investigated using the tool box of the physical sciences, including the laws of thermodynamics and the methods of energy analysis. Modern society currently uses approximately 500 exajoules (EJ = 10^18 J) of total primary energy supply (TPES) each year. This energy consumption has been increasing at roughly 2% per year for the past two hundred years. TPES is currently dominated by three non-renewable energy sources: coal, oil and gas which, together with energy from nuclear fission of uranium, make up around 85% of the energy market. Consumption of finite resources at a continuously growing rate is not sustainable in the long-term. A trend in policy direction is to seek a transition to renewable sources of energy. This thesis seeks to explore two questions: are the technical potentials of renewable energy sources enough to supply the current and/or projected demand for energy and what would be the effect on the physical resource economy of a transition to an energy supply system run entirely on renewable energy sources? The Global Energy Model using a Biophysical Approach (GEMBA) methodology developed here is compared and contrasted with other approaches that are used to study the global energy-economy system, including the standard neoclassical economic approach used in such models as MESSAGE and MARKAL. A number of meta-analyses have been conducted in support of the GEMBA model. These include: meta-analysis of historic energy production from all energy sources; meta-analysis of global energy resources for all energy sources; meta-analysis of energy-return-on-investment (EROI) for all energy sources. The GEMBA methodology uses a systems dynamic modelling approach utilising stocks and flows, feedback loops and time delays to capture the behaviour of the global energy-economy system. The system is decomposed into elements with simple behaviour that is known through energy analysis. The interaction of these elements is captured mathematically and run numerically via the systems dynamics software package, VenSim. Calibration of the model has been achieved using historic energy production data from 1800 to 2005. The core of the GEMBA methodology constitutes the description of a dynamic EROI function over the whole production cycle of an energy resource from initial development, through maturation to decline in production, in the case of non-renewable resources, or to the technical potential in the case of renewable resources. Using the GEMBA methodology, the global energy-economy system is identified as a self-regulating system. The self-regulating behaviour acts to constrain the amount of total primary energy supply that the system can produce under a renewable-only regime. A number of analyses are conducted to test the sensitivity of the system to such changes as: an increase of the technical potential of renewable resources; technological breakthroughs which would significantly increase the EROI of renewable resources; a decrease in the capital intensity of renewable resources and; an increase in the energy intensity of the economy, A statistical analysis reflecting the wide range of values of both the estimates of EROI and technical potentials of renewable energy sources has also been undertaken using a Monte Carlo approach. The results from the modelling suggest that not all levels of energy demand projected by the WEA can be supplied by an energy system running solely on renewable energy. The Monte Carlo analyses suggest that reduction in total energy yield over current (2010) levels might occur with a 20-30% possibility. The middle and high growth scenarios from the WEA are greater than 95% of all scenarios modelled, hence seem unlikely to be sustained by an energy system running solely on renewable energy. This finding has implications for the future direction of both engineering and technology research as well as for energy policy. These implications are discussed.

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Lowe, Martin. "Modelling landfill as a complex biophysical technology." Thesis, Cranfield University, 1998. http://dspace.lib.cranfield.ac.uk/handle/1826/10637.

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Concerns regarding climate change are becoming a driver behind legislation at both UK and EU levels, and also on the wider, planetary scale This is the case with emissions from landfills where the release of methane is being targeted for reduction This thesis uses an integrative approach, incorporating concepts of hierarchy from systems theory, to model landfill as a complex biophysical technology It assesses the contribution to carbon deposition and global warming of landfill through changes to that technology itself and through changes in the waste stream caused by potential waste policies The thesis develops an holistic, conceptual model of the landfill system, mapping flows and transformations of carbon within that system It further develops this conceptual model into a calculating model of landfill as a waste management technology incorporating measurements taken to provide new data and validate published data to calibrate the model It thus applies modelling techniques to a biophysical technology, producing an integrated model of the landfill that allows the knowledge gained from other research to be used to explore engineering and operational decisions on landfills The thesis includes results from measurements of the composition of household waste, and of the biochemical methane potential (BMP) of fractions of that waste It includes measurements of the residual BMP in samples of excavated waste and measurements of gas flows The main results suggest the following • Early capping of landfilled waste is important in reducing the global warming impact, • If the rate of degradation of the waste is accelerated in the drive towards sustainability, capping should be carried out even earlier if the global impact is not to be increased, • Although recycling parts of the degradable elements of the waste stream has the effect of reducing the global impact, extensive recycling has implications for landfill engineering

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TELLO, CAJIAO JOHN JAMES. "Biophysical modelling of radiation-induced chromosome aberrations." Doctoral thesis, Università degli studi di Pavia, 2019. http://hdl.handle.net/11571/1291026.

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Hanlon, Michael Richard. "Molecular modelling and biophysical characterisation of three proteins." Thesis, Birkbeck (University of London), 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.326154.

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Berardi, Andrea. "Biophysical modelling of the Astroni Nature Reserve, Naples, Italy." Thesis, University College London (University of London), 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.321946.

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Kragt, Marit Ellen. "An integrated assessment approach to linking biophysical modelling and economic valuation." Phd thesis, Canberra, ACT : The Australian National University, 2010. http://hdl.handle.net/1885/8037.

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Changes to land use and land management in Australian catchments have led to pressures on natural resources, and concerns over water quality and ecosystem health in catchment rivers and estuaries. To increase the efficiency of natural resource management (NRM) policies that address these concerns, decision makers require information about the environmental impacts, as well as the marginal costs and benefits associated with policy decisions. Including cost-benefits estimates in NRM policy assessment provides decision makers with economic information about the trade-offs between alternative NRM actions. There are, however, few studies that have assessed the complex environmental and economic trade-offs associated with changes in catchment NRM actions in a single modelling framework. This study uses an integrated assessment (IA) approach to develop a decision support model that incorporates environmental and economic dimensions of catchment NRM, for a case-study of the George catchment in Tasmania. Various (academic and non-academic) stakeholders were consulted during the model development process, to gain an understanding of the wide variety of values that may be impacted by NRM changes. Knowledge from different sources was integrated in a single framework using Bayesian network modelling techniques. The framework incorporates three major sub-models: 1. A physically based water quality model to predict the changes in sediment and nutrient loadings in the George rivers and estuary; 2. Expert opinion and Bayesian network modelling to predict the impacts of catchment NRM changes on three ecosystem attributes: riparian vegetation, rare species and estuary seagrass area; and 3. A choice experiment (CE) survey to estimate the non-market values associated with changes in George catchment ecosystem attributes. The CE study was not only aimed at assessing catchment non-market values, but also addressed methodological challenges associated with attribute level framing and cost anchoring in CE. Rather than coupling existing information and models, synchronous data collection and model development were used to ensure tailored information exchange between the different components. The IA approach to model development highlighted several challenges in synchronizing economic and scientific research. Frequent communication was required between the stakeholders involved in the project to construct a common framework for analysis. The selection of attributes that were relevant for scientists, policy makers, and CE survey respondents was a lengthy process. Agreeing on the level of modelling detail, and predicting attribute levels based on sound scientific information, also posed considerable challenges during the model development process.

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Šmít, Daniel. "Analysis of dynamical interactions of axon shafts and their biophysical modelling." Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066095/document.

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La fasciculation des axones joue un rôle essentiel dans le développement des réseaux neuronaux. Cependant, la dynamique de la fasciculation axonale, ainsi que les mécanismes biophysiques à l’œuvre dans ce processus, demeurent encore très mal compris. En vue d'étudier les mécanismes de fasciculation d'axones ex vivo, nous avons développé un système modèle simple, constitué par des explants d'épithélium olfactif de souris embryonnaires en culture, à partir desquels poussent les axones des neurones sensoriels olfactifs. Grâce à une étude en vidéomicroscopie, nous avons observé que ces axones interagissent de façon dynamique par leur fibre, à la manière de fermetures éclair pouvant se fermer ("zippering") ou s'ouvrir ("unzippering"), ce qui conduit respectivement à la fasciculation ou à la défasciculation des axones. Mettant à profit cette nouvelle préparation expérimentale pour l'étude des interactions dynamiques entre axones, nous avons développé une analyse biophysique détaillée des processus de zippering/unzippering.Nous mettons en évidence dans notre travail l'existence d'un mécanisme biophysique cohérent de contrôle des interactions locales entre fibres axonales. Ce mécanisme local est à mettre en relation avec les changements de la structure globale du réseau axonal (degré de fasciculation) qui s'opèrent sur une échelle temporelle plus longue. Enfin, nous discutons la signification fonctionnelle de nos observations et analyses, et proposons un nouveau rôles de la tension mécanique dans le développement du système nerveux : la régulation de la fasciculation des axones et, en conséquence, de la formation des cartes topologiques au sein des réseaux neuronaux While axon fasciculation plays a key role in the development of neural networks, very little is known about its dynamics and the underlying biophysical mechanisms. In a model system composed of neurons grown ex vivo from explants of embryonic mouse olfactory epithelia, we observed that axons dynamically interact with each other through their shafts, leading to zippering and unzippering behaviour that regulates their fasciculation. Taking advantage of this new preparation suitable for studying such interactions, we carried out a detailed biophysical analysis of zippering, occurring either spontaneously or induced by micromanipulations and pharmacological treatments.We show that there is a consistent mechanism which governs local interactions between axon shafts, supported by broad experimental evidence. This mechanism can be reconciled with changes in global structure of axonal network developing on slower time scale, analogically to well-studied relation between local relaxations, and topological changes and coarsening in two-dimensional liquid foams. We assess our observations and analysis in light of possible in vivo functional significance and propose a new role of mechanical tension in neural development: the regulation of axon fasciculation and consequently formation of neuronal topographic maps

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Tao, Tao. "Biophysical Modelling of the Genesis of Alternans inCardiac Intracellular Ca2+ Handling." Thesis, University of Manchester, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.504742.

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Cardiac mechanical alternans are believed to be associated with intracellular Ca2 + alternans. However, the mechanisms underlying the genesis of intracellular Ca2 + alternans are unclear. Experimental studies have shown that alternans of systolic Ca2 + under voltage clamp can be produced either by partially inhibiting the Ca2+ release mechanism or by applying small depolarising pulses. In each case the alternans relied on the appearance of propagating waves of Ca2 + release. The aim of the work in this thesis is to develop a theoretical model to understand the mechanisms underlying how the beat-to-beat alternation in the amplitude of the systolic Ca2+ transient is produced. A mathematical model of intracellular Ca2 + handling for a ventricular cardiac cell was developed as a spatially extended object, which is discretized by a group of coupled elements. Each element contains L-type and T-type Ca2 + channels, a subspace into which Ca2 + release takes place, a cytoplasmic space and sarcoplasmic reticulum (SR) release channels (RyR) and uptake sites (SERCA). Inter-element coupling is via Ca2 + diffusion between neighbouring subspaces and cytoplasm spaces. Small depolarising pulses were simulated by a sequence of step changes of cell membrane potential (20 mV) with random block on the L-type channels. Partial inhibition of the release mechanism is mimicked by applying a random reduction of the open probability of the RyR in response to a full stimulation by L type Ca2 + channels. In both cases the simulations are consistent with experimental observations and show that Ca2 + alternans can be generated and sustained through alternation of SR Ca2+ content produced by the propagating wave of Ca2 + release. However, the presented model has certain limitations. In the model, the property of L-type Ca2 + channel is described as an average effect of global current in a cardiac cell, rather than the total current of a large population of unitary L-type Ca2 + current, which is directly associated with the testing potential and which is a very important part of Ca2 + induced Ca2 + release (CICR). To conquer the limitation, an improved version of the Ca2 + handling model was developed by incorporating stochastic unitary L-type Ca2 + channels into the previous model. The improved model has a more biophysically detailed Ca2 + handling model, which can not only simulate proper unitary L-type Ca2 + influx but also produce a good quality of global L-type Ca2 + current. Like the old model the new stochastic model produced the global and regional alternans of Ca2 + transients observed in previous experimental studies as well, and agreed the key role of SR Ca2 + content to genesis of cardiac Ca2 + alternans. The study in this thesis provided novel insights into understanding the mechanisms underlying the genesis of intracellular Ca2 + alternans. In addition, the simulation study of effects of volatile anesthesics on rat ventricle has also been included in this thesis, and is presented in Appendix 1.

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Janoutová, Růžena. "Modelling 3D Forest Structure for Improved Retrieval of Forest Biophysical Properties." Doctoral thesis, Vysoké učení technické v Brně. Fakulta strojního inženýrství, 2017. http://www.nusl.cz/ntk/nusl-263358.

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Hlavním cílem práce bylo zlepšení kvantitativních odhadů vegetačních parametrů smrkových porostů pomocí spektrálních simulací trojrozměrného modelu přenosu záření. Prvně bylo potřeba vytvořit přesný 3D model smrku. Implementace přesného 3D modelu smrku pro parametrizaci celých lesních porostů je v současné době výpočetně nemožné, bylo tedy nutné tento 3D model smrku zjednodušit. Přesný 3D model smrku společně s dostupnými leteckými daty sloužil pro nalezení optimálního zjednodušení. Optimální model vedl ke kompromisu mezi výpočetní náročností a přesností výsledné odrazivosti z modelu přenosu záření. Následně byl optimální model smrku využit pro odhady vegetačních parametrů ze satelitních snímků. Přesnost odhadů byla ověřena oproti pozemním měřením odhadovaných parametrů. Na závěr byly porovnány výsledky z odhadů vegetačních parametrů pomocí optimálního 3D modelu smrku s výsledky z tradičního přístupu pomocí modelů stromu s geometricky jednodušími tvary korun.

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Howells, James Anthony. "Biophysical Determinants of the Behaviour of Human Myelinated Axons." Thesis, The University of Sydney, 2013. http://hdl.handle.net/2123/10268.

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This thesis investigates the role of the hyperpolarization-activated current, Ih, on the excitability of human axons. It exploits the unique characteristics of the underlying hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels to improve existing and create new techniques for studying Ih. An isolated amplifier with low-noise and high common-mode rejection was developed, and threshold tracking techniques were modified to allow the measurement of the excitability of low-threshold sensory axons and of cutaneous afferents close to their receptors. These developments open up the possibility of studying changes in polyneuropathies, where symptoms and possibly the underlying pathology are more apparent distally in the limbs. Strong and long-lasting hyperpolarization was used to open more HCN channels and to examine their contribution to the excitability of motor and sensory axons. A mathematical model of myelinated motor axons was adapted to account for the response to strong and long-lasting hyperpolarization. Without structural changes the model was then modified to fit the observed excitability of sensory axons. Changes in the excitability and safety margin during focal hyperthermia were studied in both motor and sensory axons of the median nerve, and the underlying mechanisms were explored using the new mathematical model. Finally, the involvement of Ih in the frequency preference of oscillation in human axons was investigated by developing resonance techniques that have hitherto never been used to study axonal function.

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Valentine, Ronan. "Biophysical aspects of photodynamic therapy." Thesis, University of St Andrews, 2011. http://hdl.handle.net/10023/2471.

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Photodynamic therapy (PDT) is a multimodality cancer treatment available for the palliation or eradication of systemic and cutaneous malignancies. In this thesis, the application of PDT is for the treatment of non-melanoma skin cancer (NMSC). While PDT has a well-documented track record, there are, at this time no significant indicators to suggest the superiority of one treatment regime over the next. The motivation for this work is to provide additional evidence pertaining to PDT treatment variables, and to assist in optimising PDT treatment regimes. One such variable is the treatment light dose. Determining the light dose more accurately would assist in optimising treatment schedules. Furthermore, choice of photosensitiser pro-drug type and application times still lack an evidence base. To address issues concerning treatment parameters, fluorescence spectroscopy – a valuable optical diagnostic technique – was used. Monitoring the in vivo PpIX fluorescence and photobleaching during PDT was employed to provide information pertaining to the progression of treatment. This was demonstrated by performing a clinical study at the Photobiology Unit, Ninewells Hospital and Medical School, Dundee. Two different photosensitiser pro-drugs – either 5-aminolaevulinic acid (ALA) or its methyl ester (MAL) – were investigated and based on the fluorescence and pain data recorded both may be equally suitable for topical PDT. During PDT, surface fluorescence is observed to diminish with time – due to photobleaching – although cancerous cells may continue to be destroyed deep down in the tissue. Therefore, it is difficult to ascertain what is happening at depth in the tumour. This raised the questions; How long after surface PpIX fluorescence has diminished is the PDT treatment still effective and to what depths below the surface is effective treatment provided? In order to address these important questions, a three-dimensional (3D) Monte Carlo radiation transfer (MCRT) model was used to compute the light dose and the ¹O₂ production within a tumour, and the PpIX fluorescence emission from the tumour. An implicit dosimetry approach based on a single parameter – fluorescence photobleaching – was used in order to determine the ¹O₂ generation, which is assumed to be related to tissue damage. Findings from our model recommended administering a larger treatment light dose, advocating an increase in the treatment time after surface PpIX fluorescence has diminished. This increase may ultimately assist in optimising PDT treatment regimes, particularly at depth within tumours.

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Piechnik, Stefan K. "A mathematical and biophysical modelling of cerebral blood flow and cerebrospinal fluid dynamics." Thesis, University of Cambridge, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.269226.

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Talathi, Sachin S. "Biophysical modelling of synaptic plasticity and its function in the dynamics of neuronal networks." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC IP addresses, 2006. http://wwwlib.umi.com/cr/ucsd/fullcit?p3214710.

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Thesis (Ph. D.)--University of California, San Diego, 2006. Title from first page of PDF file (viewed July 10, 2006). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (p. 147-155).

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Ni, Haibo. "Biophysical modelling of functional impacts of potassium channel mutations on human atrial and ventricular dynamics." Thesis, University of Manchester, 2017. https://www.research.manchester.ac.uk/portal/en/theses/biophysical-modelling-of-functional-impacts-of-potassium-channel-mutations-on-human-atrial-and-ventricular-dynamics(3372fd6a-850b-4f7d-893a-e2da28269ba8).html.

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Atrial fibrillation (AF) is the most common cardiac arrhythmia causing morbidity and mortality. Despite recent advances, developing effective and safe anti-AF pharmaceutical therapies remains challenging and is prone to adverse effects in the ventricles. Atrial-selective therapies are promising in managing AF. A better understanding of the role of the atrial-specific ion channels in the atrial arrhythmogenesis and contractility, as well as the anti-AF effects of blocking these channels is of interests. Also, a 3D ventricle-torso model capable of modelling ventricular electrical activities and the resulting electrocardiogram (ECG) is a valuable tool in evaluating the selectiveness and safety of an anti-AF pharmaceutical therapy. In part I, the role of an atrial-specific ion channel, IKur, in atrial electrical and mechanical activities and the potential of the current as a pharmaceutical target for anti-AF therapies were investigated in silico. The role of IKur in atrial arrhythmogenesis and mechanical contraction was revealed by elucidating the functional impacts of the KCNA5 mutations exerting either gain- or loss-in-function, on the atria. First, novel IKur models were developed and incorporated into multiscale biophysical models of human atrial electrophysiology to assess the effects of mutated IKur on atrial electrical dynamics. Then, a family of single cell human atrial electromechanical models was developed and incorporated into an updated 3D anatomical electromechanical model of human atria to clarify the effects of mutated IKur on the atrial contractile function. Finally, the antiarrhythmic effect of IKur block was assessed together with INa and other K+-current block. It was shown that the gain-of-function in IKur impaired atrial contractility and promoted atrial arrhythmogenesis by shortening the APD, whereas the down-regulated IKur exerted positive inotropic effects and increased the susceptibility of the atria to the genesis of early-afterdepolarisations. Both simulated IKur and INa block in human-AF demonstrated antiarrhythmic effects; the multi-channel block exerted synergistic anti-AF effects and enhanced the AF-selectivity of INa inhibitions. In Part II, a human ventricle-torso model was developed through proposing a new family of single cell ventricular models accounting for transmural, apicobasal and interventricular electrical heterogeneities and integrating an updated 3D biophysical and anatomical model of human ventricles with a heterogeneous anatomical model of a human torso. First, using the model, the role of heterogeneities in the genesis of T-wave was revealed. Then, ECG manifestations of bundle branch block and ventricular ischaemia were simulated. Finally, the platform was applied to investigate the impact of a long-QT-linked mutation (KCNQ1-G269S) on the ventricles and ECG. Good agreement between simulated and experimental/clinical ECG was reached under both normal and diseased conditions. It was shown that the apicobasal heterogeneity had a more pronounced effect on the T-wave than other heterogeneities. Simulations of the KCNQ1-G269S elucidated the causal link between the mutation and ECG manifestations of the patients.

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Khanna, Neha, and Neha Khanna@mdbc gov au. "Investigation of phytoplankton dynamics using time-series analysis of biophysical parameters in Gippsland Lakes, South-eastern Australia." RMIT University. Civil, Environmental and Chemical Engineering, 2007. http://adt.lib.rmit.edu.au/adt/public/adt-VIT20080226.123435.

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There is a need for ecological modelling to help understand the dynamics in ecological systems, and thus aid management decisions to maintain or improve the quality of the ecological systems. This research focuses on non linear statistical modelling of observations from an estuarine system, Gippsland Lakes, on the south-eastern coast of Australia. Feed forward neural networks are used to model chlorophyll time series from a fixed monitoring station at Point King. The research proposes a systematic approach to modelling in ecology using feed forward neural networks, to ensure: (a) that results are reliable, (b) to improve the understanding of dynamics in the ecological system, and (c) to obtain a prediction, if possible. An objective filtering algorithm to enable modelling is presented. Sensitivity analysis techniques are compared to select the most appropriate technique for ecological models. The research generated a chronological profile of relationships between biophysical parameters and chlorophyll level for different seasons. A sensitivity analysis of the models was used to understand how the significance of the biophysical parameters changes as the time difference between the input and predicted value changes. The results show that filtering improves modelling without introducing any noticeable bias. Partial derivative method is found to be the most appropriate technique for sensitivity analysis of ecological feed forward neural networks models. Feed forward neural networks show potential for prediction when modelled on an appropriate time series. Feed forward neural networks also show capability to increase understanding of the ecological environment. In this research, it can be seen that vertical gradient and temperature are important for chlorophyll levels at Point King at time scales from a few hours to a few days. The importance of chlorophyll level at any time to chlorophyll levels in the future reduces as the time difference between them increases.

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Hall, Zoe Lauren. "Protein complexes in the gas phase : structural insights from ion mobility-mass spectrometry and computational modelling." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:a958f616-e37f-42e2-bf57-a38d58388b0c.

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Structure determination of macromolecular protein assemblies remains a challenge for well-established experimental methods. In this thesis, an emerging structural technique, ion mobility-mass spectrometry (IM-MS) is explored. An assessment of collision cross section (CCS) measurement accuracy using travelling-wave IM (TWIMS) instrumentation was carried out (Chapter 3). Through the collation of a protein complex CCS database and the development of a calibration framework for TWIMS, significant improvements to CCS measurement accuracy have been achieved. Next, the advantages and limitations of using IM-MS to generate restraints for structure characterisation were explored. Computational tools designed to exploit IM-MS data for structural modelling were developed and tested on a training set of systems (Chapter 4). These include two heteromeric protein complexes, and an oligomeric intermediate involved in beta-2-microglobulin aggregation. Further structural information can be attained by using gas-phase dissociation techniques, such as collision-induced dissociation (CID). The effects of charge state on CCS and the gas-phase dissociation pathway of complexes were investigated (Chapter 5). This highlighted the possibility of using CID in conjunction with supercharging to manipulate dissociation pathways to achieve more useful structural information. Finally, the gas-phase structures of globular and intrinsically disordered protein complexes were probed by IM-MS and molecular dynamics (MD) simulations (Chapter 6). Experimental observations were recapitulated remarkably closely by simulations, including gas-phase structural collapse and the ejection of monomer subunits when the energy of the system was increased sufficiently. Overall, this research has contributed to the IM-MS field by providing the framework for improved CCS measurements of large protein complexes and the use of restraints from IM-MS for structural modelling. Significantly, IM-MS has been used in combination with charge manipulation, CID and MD simulations to reveal further insights into the gas-phase structures, stabilities and dissociation pathways of multimeric protein complexes.

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Sulieman, Hussein Mohamed. "Mapping and Modelling of Vegetation Changes in the Southern Gadarif Region, Sudan, Using Remote Sensing: Land-Use Impacts on Biophysical Processes." Doctoral thesis, Dresden TUDpress, 2007. http://deposit.d-nb.de/cgi-bin/dokserv?id=3058481&prov=M&dok_var=1&dok_ext=htm.

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Babi, Almenar Javier. "Characterisation, biophysical modelling and monetary valuation of urban nature-based solutions as a support tool for urban planning and landscape design." Doctoral thesis, Università degli studi di Trento, 2021. http://hdl.handle.net/11572/288810.

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The recognition of nature in the resolution of societal challenges has been growing in relevance. This recognition has been associated with the development of new concepts from science and policy such as natural capital, ecosystem services, green infrastructure, and more recently Nature-Based Solutions (NBS). NBS intends to address societal challenges in an effective and adaptive form providing economic, social, and environmental benefits. The overall aim of this PhD thesis is to develop an environmental and economic assessment of NBS for highly urbanised territories based on rationales and models underpinning ecosystem services, urban/landscape ecology, and life cycle thinking approaches. This combined evaluation approach would help to better understand if NBS are cost-effective or not. The aim is developed according to four specific objectives. The first objective corresponds to the characterisation of NBS in relation to urban contexts and the problematics that they can help to address or mitigate. To achieve this objective a critical review on the study of the relationship between NBS, ecosystem services (ES) and urban challenges (UC) was developed. As a main output, a graph of plausible cause-effect relationships between NBS, ES and UC is obtained. The graph represents a first step to support sustainable urban planning, moving from problems (i.e. urban challenges) to actions (i.e. NBS) to resolutions (i.e. ES). The second objective corresponds to the definition of an adequate set of biophysical and monetary assessment methods and indicators to evaluate the value of NBS in urbanised contexts. To achieve this objective, a review of existing methods on ecosystem services valuation, life cycle cost analysis and life-cycle assessment are developed. The review takes into account specific constraints such as easiness to use and availability of data. At the end, potential methods and indicators were selected, which will be later integrated in the combined assessment framework. The third objective corresponds to the design of a combined assessment framework integrating methods from life cycle assessment, landscape/urban ecology and ecosystem services that quantifies the environmental and economic value of NBS informing about the cost-effectiveness of its entire life cycle. To achieve this objective, a conceptual framework is developed. From it, a system dynamics model of ecosystem (dis)services is developed and coupled with a life cycle assessment method. The combined evaluation is tested with a relevant NBS type (i.e. urban forest) in a case study in the metropolitan area of Madrid. The fourth objective is the development of a decision support (DSS) tool that integrates the assessment framework as part of iterative design processes in urban planning and landscape design. The DSS intends to enhance the interrelation between science, policy and planning/design. To achieve this objective a user-friendly web-based prototype DSS on NBS, called NBenefit$®, is developed. The prototype DSS provides the user a simple form of quantifying the provision of multiple ES and costs over the entire life cycle (implementation, operational life, and end-of-life) of NBS. This thesis contributed to the characterisation of NBS and its environmental and economic assessment to inform urban planning and landscape design processes, allowing decisions that are more informed. Il riconoscimento della natura nella risoluzione delle sfide sociali è diventato sempre più importante. Questo riconoscimento è stato associato allo sviluppo di nuovi concetti provenienti dalla scienza e dalla politica, come il capitale naturale, i servizi ecosistemici, le infrastrutture verdi e, più recentemente, le soluzioni basate sulla natura (NBS). NBS intende affrontare le sfide della società in una forma efficace e adattabile fornendo benefici economici, sociali e ambientali. Lo scopo di ricerca di questa tesi di dottorato è quello di sviluppare una valutazione ambientale ed economica delle NBS per territori altamente urbanizzati basata su logiche e modelli che hanno alla base i servizi ecosistemici, l'ecologia urbana e paesaggistica e degli approcci di approcio life cycle. Questo quadro di valutazione combinato aiuterebbe a capire meglio se le NBS sono costo effetive e se contribuiscono a uno sviluppo resiliente e sostenibile. Questo scopo di ricerca è sviluppato secondo quattro obiettivi specifici. Il primo obiettivo corrisponde alla caratterizzazione delle NBS in relazione ai contesti urbani e alle problematiche che possono aiutare ad affrontare o mitigare. Per raggiungere questo obiettivo è stata sviluppata una revisione critica dell letteratura sullo studio della relazione tra NBS, servizi ecosistemici (ES) e sfide urbane (UC). Come risultato principale, si ottiene un grafico delle relazioni causa-effetto plausibili tra NBS, ES ed UC. Il grafico rappresenta un primo passo per supportare la pianificazione urbana sostenibile, passando dai problemi (es. UC) alle azioni (es. NBS) alle risoluzioni (es. ES). Il secondo obiettivo corrisponde alla definizione di un set di metodi e indicatori di valutazione biofisica e monetaria adeguate per valutare il valore della NBS in contesti urbanizzati. Per raggiungere questo obiettivo, viene sviluppata una revisione dei metodi esistenti sulla valutazione dei servizi ecosistemici, l'analisi dei costi del ciclo di vita e la valutazione del ciclo di vita. La revisione tiene conto di vincoli specifici come la facilità d'uso e la disponibilità dei dati. Alla fine, sono stati selezionati potenziali metodi e indicatori, che saranno successivamente integrati nel quadro di valutazione combinato. Il terzo obiettivo corrisponde alla progettazione del quadro di valutazione combinato, integrando metodi di valutazione del ciclo di vita, ecologia paesaggistica / urbana e servizi ecosistemici che quantifica il valore ambientale ed economico della NBS informando sull'efficacia in termini di costi del suo intero ciclo di vita. Per raggiungere questo obiettivo, prima viene sviluppato un quadro concettuale. Da esso, viene sviluppato un modello di dinamica di sistemi per calcolare i servizi (e disservici) ecosistemici, il quale è interrelazionato con un metodo di valutazione life cycle. Questa valutazione combinata viene testata con un tipo di NBS pertinente (foresta urbana) in un caso di studio nell'area metropolitana di Madrid. Il quarto obiettivo è lo sviluppo di uno strumento di supporto decisionale (DSS) che integri il quadro di valutazione come parte dei processi di progettazione iterativa nella pianificazione urbana e nella progettazione del paesaggio. Il DSS intende migliorare l'interrelazione tra scienza, politica e pianificazione / progettazione. Per raggiungere questo obiettivo è stato sviluppato Nbenefit$® un prototipo di DSS online per la valutazzione NBS di facile uso. Il prototipo DSS fornisce all'utente una forma semplice per quantificare multipli ES e costi (internalizatti o no) durante l'intero ciclo di vita (implementazione, vita operativa e fine vita) del NBS. In conclusione, questa tesi ha contribuito alla caratterizzazione di NBS e alla sua valutazione ambientale ed economica per informare i processi di pianificazione urbana e progettazione del paesaggio, consentendo decisioni più informate.

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22

Babi, Almenar Javier. "Characterisation, biophysical modelling and monetary valuation of urban nature-based solutions as a support tool for urban planning and landscape design." Doctoral thesis, Università degli studi di Trento, 2021. http://hdl.handle.net/11572/288810.

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The recognition of nature in the resolution of societal challenges has been growing in relevance. This recognition has been associated with the development of new concepts from science and policy such as natural capital, ecosystem services, green infrastructure, and more recently Nature-Based Solutions (NBS). NBS intends to address societal challenges in an effective and adaptive form providing economic, social, and environmental benefits. The overall aim of this PhD thesis is to develop an environmental and economic assessment of NBS for highly urbanised territories based on rationales and models underpinning ecosystem services, urban/landscape ecology, and life cycle thinking approaches. This combined evaluation approach would help to better understand if NBS are cost-effective or not. The aim is developed according to four specific objectives. The first objective corresponds to the characterisation of NBS in relation to urban contexts and the problematics that they can help to address or mitigate. To achieve this objective a critical review on the study of the relationship between NBS, ecosystem services (ES) and urban challenges (UC) was developed. As a main output, a graph of plausible cause-effect relationships between NBS, ES and UC is obtained. The graph represents a first step to support sustainable urban planning, moving from problems (i.e. urban challenges) to actions (i.e. NBS) to resolutions (i.e. ES). The second objective corresponds to the definition of an adequate set of biophysical and monetary assessment methods and indicators to evaluate the value of NBS in urbanised contexts. To achieve this objective, a review of existing methods on ecosystem services valuation, life cycle cost analysis and life-cycle assessment are developed. The review takes into account specific constraints such as easiness to use and availability of data. At the end, potential methods and indicators were selected, which will be later integrated in the combined assessment framework. The third objective corresponds to the design of a combined assessment framework integrating methods from life cycle assessment, landscape/urban ecology and ecosystem services that quantifies the environmental and economic value of NBS informing about the cost-effectiveness of its entire life cycle. To achieve this objective, a conceptual framework is developed. From it, a system dynamics model of ecosystem (dis)services is developed and coupled with a life cycle assessment method. The combined evaluation is tested with a relevant NBS type (i.e. urban forest) in a case study in the metropolitan area of Madrid. The fourth objective is the development of a decision support (DSS) tool that integrates the assessment framework as part of iterative design processes in urban planning and landscape design. The DSS intends to enhance the interrelation between science, policy and planning/design. To achieve this objective a user-friendly web-based prototype DSS on NBS, called NBenefit$®, is developed. The prototype DSS provides the user a simple form of quantifying the provision of multiple ES and costs over the entire life cycle (implementation, operational life, and end-of-life) of NBS. This thesis contributed to the characterisation of NBS and its environmental and economic assessment to inform urban planning and landscape design processes, allowing decisions that are more informed. Il riconoscimento della natura nella risoluzione delle sfide sociali è diventato sempre più importante. Questo riconoscimento è stato associato allo sviluppo di nuovi concetti provenienti dalla scienza e dalla politica, come il capitale naturale, i servizi ecosistemici, le infrastrutture verdi e, più recentemente, le soluzioni basate sulla natura (NBS). NBS intende affrontare le sfide della società in una forma efficace e adattabile fornendo benefici economici, sociali e ambientali. Lo scopo di ricerca di questa tesi di dottorato è quello di sviluppare una valutazione ambientale ed economica delle NBS per territori altamente urbanizzati basata su logiche e modelli che hanno alla base i servizi ecosistemici, l'ecologia urbana e paesaggistica e degli approcci di approcio life cycle. Questo quadro di valutazione combinato aiuterebbe a capire meglio se le NBS sono costo effetive e se contribuiscono a uno sviluppo resiliente e sostenibile. Questo scopo di ricerca è sviluppato secondo quattro obiettivi specifici. Il primo obiettivo corrisponde alla caratterizzazione delle NBS in relazione ai contesti urbani e alle problematiche che possono aiutare ad affrontare o mitigare. Per raggiungere questo obiettivo è stata sviluppata una revisione critica dell letteratura sullo studio della relazione tra NBS, servizi ecosistemici (ES) e sfide urbane (UC). Come risultato principale, si ottiene un grafico delle relazioni causa-effetto plausibili tra NBS, ES ed UC. Il grafico rappresenta un primo passo per supportare la pianificazione urbana sostenibile, passando dai problemi (es. UC) alle azioni (es. NBS) alle risoluzioni (es. ES). Il secondo obiettivo corrisponde alla definizione di un set di metodi e indicatori di valutazione biofisica e monetaria adeguate per valutare il valore della NBS in contesti urbanizzati. Per raggiungere questo obiettivo, viene sviluppata una revisione dei metodi esistenti sulla valutazione dei servizi ecosistemici, l'analisi dei costi del ciclo di vita e la valutazione del ciclo di vita. La revisione tiene conto di vincoli specifici come la facilità d'uso e la disponibilità dei dati. Alla fine, sono stati selezionati potenziali metodi e indicatori, che saranno successivamente integrati nel quadro di valutazione combinato. Il terzo obiettivo corrisponde alla progettazione del quadro di valutazione combinato, integrando metodi di valutazione del ciclo di vita, ecologia paesaggistica / urbana e servizi ecosistemici che quantifica il valore ambientale ed economico della NBS informando sull'efficacia in termini di costi del suo intero ciclo di vita. Per raggiungere questo obiettivo, prima viene sviluppato un quadro concettuale. Da esso, viene sviluppato un modello di dinamica di sistemi per calcolare i servizi (e disservici) ecosistemici, il quale è interrelazionato con un metodo di valutazione life cycle. Questa valutazione combinata viene testata con un tipo di NBS pertinente (foresta urbana) in un caso di studio nell'area metropolitana di Madrid. Il quarto obiettivo è lo sviluppo di uno strumento di supporto decisionale (DSS) che integri il quadro di valutazione come parte dei processi di progettazione iterativa nella pianificazione urbana e nella progettazione del paesaggio. Il DSS intende migliorare l'interrelazione tra scienza, politica e pianificazione / progettazione. Per raggiungere questo obiettivo è stato sviluppato Nbenefit$® un prototipo di DSS online per la valutazzione NBS di facile uso. Il prototipo DSS fornisce all'utente una forma semplice per quantificare multipli ES e costi (internalizatti o no) durante l'intero ciclo di vita (implementazione, vita operativa e fine vita) del NBS. In conclusione, questa tesi ha contribuito alla caratterizzazione di NBS e alla sua valutazione ambientale ed economica per informare i processi di pianificazione urbana e progettazione del paesaggio, consentendo decisioni più informate.

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23

Hunt, Laurence T. "Modelling human decision under risk and uncertainty." Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:244ce799-7397-4698-8dac-c8ca5d0b3e28.

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Humans are unique in their ability to flexibly and rapidly adapt their behaviour and select courses of action that lead to future reward. Several ‘component processes’ must be implemented by the human brain in order to facilitate this behaviour. This thesis examines two such components; (i) the neural substrates supporting action selection during value- guided choice using magnetoencephalography (MEG), and (ii) learning the value of environmental stimuli and other people’s actions using functional magnetic resonance imaging (fMRI). In both situations, it is helpful to formally model the underlying component process, as this generates predictions of trial-to-trial variability in the signal from a brain region involved in its implementation. In the case of value-guided action selection, a biophysically realistic implementation of a drift diffusion model is used. Using this model, it is predicted that there are specific times and frequency bands at which correlates of value are seen. Firstly, there are correlates of the overall value of the two presented options, and secondly the difference in value between the options. Both correlates should be observed in the local field potential, which is closely related to the signal measured using MEG. Importantly, the content of these predictions is quite distinct from the function of the model circuit, which is to transform inputs relating to the value of each option into a categorical decision. In the case of social learning, the same reinforcement learning model is used to track both the value of two stimuli that the subject can choose between, and the advice of a confederate who is playing alongside them. As the confederate advice is actually delivered by a computer, it is possible to keep prediction error and learning rate terms for stimuli and advice orthogonal to one another, and so look for neural correlates of both social and non-social learning in the same fMRI data. Correlates of intentional inference are found in a network of brain regions previously implicated in social cognition, notably the dorsomedial prefrontal cortex, the right temporoparietal junction, and the anterior cingulate gyrus.

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24

Sulieman, Hussein Mohamed [Verfasser]. "Mapping and modelling of vegetation changes in the Southern Gadarif Region, Sudan, using remote sensing : land-use impacts on biophysical processes / Hussein Mohamed Sulieman." Dresden : TUDpress, 2008. http://d-nb.info/997493739/34.

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25

Sulieman, Hussein Mohamed. "Mapping and Modelling of Vegetation Changes in the Southern Gadarif Region, Sudan, Using Remote Sensing." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2008. http://nbn-resolving.de/urn:nbn:de:bsz:14-ds-1199964393472-79860.

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The study was conducted at the vicinity of the rural town of Doka in an area of about 55 x 40 km2. The aim of the study was to map and model the influences of the introduction of mechanized rain-fed agriculture and its rapid expansion on the natural vegetation in the southern Gadarif Region. To achieve these objectives the study utilized a series of techniques. Beside the intensive use of remote sensing imagery, interviews with key informants and farmers as well as detailed field surveys were carried out. Multi-temporal analyses of remote sensing imagery showed that during the seventies the average natural vegetation clearing rate increased most rapidly and then began to slow down. Farmers are aware that land degradation, in various forms, is taking place on their cultivated agricultural land. This is based on their perception and the interpretation of indicators such as weed infestation, reduced soil fertility and soil compaction. Continuous cropping, mono-cropping, rainfall shortage and the use of inferior seeds were the main reasons of land degradation indicated by the farmers. Abandonment of agricultural land to restore soil fertility is a common practice among farmers in the Gadarif Region. The study proved that the subsequent natural regeneration of plant species and the vegetation development on abandoned agricultural land are subject to the previous cultivation period and the duration of the fallow. The current regeneration capacity of the abandoned land may not be sufficient to reach full restoration of the previous vegetation climax except for some pockets which received more regenerative resources. Field surveys in conjunction with remotely sensed and topographic data have the potential to explain the restoration and rehabilitation patterns of degraded/abandoned agricultural land to a good extent. The findings of the study seem to be representative not only for the whole Gadarif Region or other areas in Sudan, but also for other regions in the Sahel Zone with similar problems and environmental and social conditions. One of the most practical conservation approaches is to let farmers play an active role in managing their abandoned land. Such management aims to allow for a certain level of use and benefits while maintaining the natural vegetation development on theses area in order to achieve maximal restoration. Although the study investigated the vegetation development in abandoned mechanized rainfed agricultural land, a full understanding of the path-way needs surveys that include more types of abandoned land and investigation of the effects of other local environmental factors (e.g. fire, grazing, distance from forests etc.) for more than one season.

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26

Poignant, Floriane. "Physical, chemical and biological modelling for gold nanoparticle-enhanced radiation therapy : towards a better understanding and optimization of the radiosensitizing effect." Thesis, Lyon, 2019. http://www.theses.fr/2019LYSE1160.

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En radiothérapie, les nanoparticules faites de métaux lourds telles que les nanoparticules l’or (AuNPs) ont démontré des propriétés radiosensibilisantes particulièrement prometteuses. Une augmentation de la dose et du nombre de radicaux produits, à échelle tumorale (effet photoélectrique) et à échelle sub-cellulaire (électrons Auger) pourraient être responsables d’une partie des effets pour les rayons X de basse énergie. Dans le cadre de cette thèse, nous proposons d'étudier ces mécanismes physiques et chimiques précoces par des outils de simulation, afin de mieux les quantifier et comprendre leur impact sur la survie cellulaire. Nous avons d’abord finalisé et validé une simulation Monte Carlo développée pour suivre les électrons jusqu’à très basse énergie à la fois dans l’eau (meV) et dans l’or (eV). Nous avons obtenu de bons résultats pour l’or en comparant nos données avec des données expérimentales de la littérature, en terme de production d’électrons et de perte d’énergie. Nous avons utilisé cet outil de simulation pour quantifier l’énergie déposée dans des nanocibles situées près d’une AuNP, qui est corrélée à la probabilité de générer des dommages. Cette étude a nécessité d’importantes optimisations, afin d’atteindre des temps de calculs raisonnables. Nous avons montré une augmentation significative de la probabilité d’avoir un dépôt d’énergie dans la nanocible supérieur à une énergie seuil, dans un rayon de 200 nm autour de la AuNP, ce qui suggère qu’une AuNP pourrait efficacement détruire des cibles biologiques situées dans sa périphérie. Nous avons ensuite utilisé la simulation pour quantifier des effets chimiques. A échelle macroscopique, nous avons estimé l'augmentation de la quantité de radicaux libres produits en présence d’une concentration d’AuNPs. Nous avons également comparé la distribution radiale des espèces chimiques d’une nanoparticule d’or ionisée, à celle d’une nanoparticule d’eau ionisée. Si le nombre total d'espèces chimiques par ionisation était en moyenne plus important pour l'or que pour l'eau, le nombre d’espèces chimiques produites en périphérie de la nanoparticule n’était pas systématiquement supérieur pour l’or par rapport à l’eau. Cela suggère que l’effet de la AuNP dans sa périphérie réside surtout dans l’augmentation de la probabilité d’avoir une ionisation. Nous avons également étudié plusieurs scénarios pour expliquer l’augmentation expérimentale inattendue de la production d’espèces fluorescentes lors de l’irradiation d’une solution d’AuNPs et de coumarine. Notre étude suggère qu’un scénario plausible pouvant expliquer les observations expérimentales est l’interférence entre une AuNP et une des molécules intermédiaires produites suite à la réaction entre la coumarine et le radical hydroxyle. Pour finir, nous avons injecté les résultats des simulations dans le modèle biophysique NanOx, développé à l’origine à l’IPNL pour calculer des doses biologiques en hadronthérapie, afin de prédire la survie cellulaire en présence de AuNPs. Nous avons aussi implémenté le Local Effect Model (LEM), principal modèle biophysique utilisé dans le contexte des nanoparticules. Pour le LEM, nous nous sommes appuyés sur plusieurs approches dosimétriques proposées dans la littérature. Pour un système simpliste où les AuNPs étaient distribuées de façon homogène dans la cellule, nous avons montré que, selon l’approche dosimétrique, les prédictions de survies du LEM étaient significativement différentes. De plus, nous avons obtenu une augmentation de la mort cellulaire avec NanOx qui était due uniquement à l’augmentation macroscopique du dépôt de dose. Nous n’avons obtenu aucun effet supplémentaire dû aux électrons Auger, en contradiction avec les prédictions du LEM. Cette étude suggère que les modèles actuels proposés pour prédire l'effet radiosensibilisant des AuNPs doivent être améliorés pour être prédictifs, en prenant par exemple en compte de potentiels mécanismes biologiques mis en évidence par l'expérience In radiation therapy, high-Z nanoparticles such as gold nanoparticles (GNPs) have shown particularly promising radiosensitizing properties. At an early stage, an increase in dose deposition and free radicals production throughout the tumour (photoelectric effect) and at sub-cellular scale (Auger cascade) might be responsible for part of the effect for low-energy X-rays. In this Ph.D work, we propose to study these early mechanisms with simulation tools, in order to better quantify them and better understand their impact on cell survival. We first finalised and validated Monte Carlo (MC) models, developed to track electrons down to low energy both in water (meV) and gold (eV). The comparison of theoretical predictions with available experimental data in the literature for gold provided good results, both in terms of secondary electron production and energy loss. This code allowed us to quantify the energy deposited in nanotargets located near the GNP, which is correlated with the probability to generate damages. This study required important optimisations in order to achieve reasonable computing time. We showed a significant increase of the probability of having an energy deposition in the nanotarget larger than a threshold, within 200 nm around the GNP, suggesting that GNPs may be particularly efficient at destroying biological nanotargets in its vicinity. The MC simulation was then used to quantify some chemical effects. At the macroscale, we quantified the increase of free radicals production for a concentration of GNPs. We also compared the radial distribution of chemical species following the ionisation of either a gold nanoparticle or a water nanoparticle. We showed that following an ionization, the average number of chemical species produced is higher for gold compared to water. However, in the vicinity of the nanoparticle, the number of chemical species was not necessarily higher for gold compared to water. This suggests that the effect of GNPs in its vicinity mostly comes from the increase of the probability of having an ionisation. We also studied several scenarios to explain the unexpectedly high experimental increase of the production of fluorescent molecules during the irradiation of a colloidal solution of GNPs and coumarin. Our study suggests that a plausible scenario to explain experimental measurements would be that GNPs interfere with an intermediate molecule, produced following the reaction between a coumarine molecule and a hydroxyl radical. During the last step of this Ph.D work, we injected our MC results in the biophysical model NanOx, originally developed at IPNL to calculate the biological dose in hadrontherapy, to predict cell survival in presence of GNPs. In addition, we implemented the Local Effect Model (LEM), currently the main biophysical model implemented for GNP-enhanced radiation therapy, to compare the NanOx and the LEM predictions with each other. In order to estimate cell survival with the LEM, we used various dosimetric approaches that were proposed in the literature. For a simple system where GNPs were homogeneously distributed in the cell, we showed that the LEM had different outcomes with regard to cell survival, depending on the dosimetric approach. In addition, we obtained an increase of cell death with the biophysical model NanOx that was purely due to the increase of the macroscopic dose. We did not obtain an increased biological effectiveness due to Auger electrons, which comes in contradiction with the LEM predictions. This study suggests that the current biophysical models available to predict the radiosensitizing effect of GNPs must be improved to be predictive. This may be done, for instance, by accounting for potential biological mechanisms evidenced by experimental works

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27

Velic, Amar. "Mechanics of bacterial interaction and geometry enhancement on nanopatterned surfaces." Thesis, Queensland University of Technology, 2021. https://eprints.qut.edu.au/212531/1/Amar_Velic_Thesis.pdf.

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This thesis investigated the deformation and resulting antibacterial activity of bacteria on nanopatterned surfaces, to understand how these surfaces elicit their physical killing action and how they can be optimised. Through finite element and experimental investigation, it was demonstrated that nanopatterned surfaces kill bacteria at their tips by delivering lethal deformation which can be enhanced by reducing key nanopattern dimensions. The findings help towards the development of a new generation antimicrobial materials to combat biofilm infection, fomite transmission and emerging resistance.

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28

Fernandes, Gonçalo. "Imaging transcription in living embryos to decipher the robustness of patterning." Electronic Thesis or Diss., Université Paris sciences et lettres, 2022. http://www.theses.fr/2022UPSLS025.

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Au cours du développement, les gradients morphogénétiques fournissent l’information positionnelle nécessaire à l’établissement des axes de polarité. Si l’importance de ces gradients est bien établie, la façon dont ils assurent la reproductibilité des patrons d’expression malgré la nature stochastique de la transcription reste énigmatique.Pour répondre à cette question, j’étudie l’établissement de l’axe antéro-postérieur (AP) de l’embryon de drosophile, sous contrôle de Bicoid (Bcd), un facteur de transcription et morphogène bien connu. Les ARNs de bcd sont exprimés maternellement et ancrés au pôle antérieur de l’ovocyte. Après la ponte, ces ARNs sont traduits en protéines, qui diffusent dans le cytoplasme pour former un gradient de concentration exponentiel avec son maximum au pôle antérieur. Un modèle simple propose que le destin de chaque cellule le long de l’axe est déterminé par la concentration de Bcd qu’elle reçoit. Toutefois, de nombreux débats ont remis en question la possibilité que les patrons d’expression induits par Bcd résultent uniquement des propriétés de diffusion et d’interaction des protéines Bcd avec leurs séquences cibles.L’objectif de ma thèse était de comprendre le rôle précis de Bcd dans l’expression de son gène cible principal, hunchback (hb). Pour cela, j’ai adapté à des gènes rapporteurs synthétiques, le système MS2-MCP, qui permet l’étiquetage fluorescent des ARN et l’analyse quantitative de la dynamique transcriptionnelle avec une forte résolution spatio-temporelle dans les embryons vivants. Dans ces rapporteurs, la séquence MS2 est contrôlée par un promoteur minimal contenant aussi les sites de fixation pour Bcd ou ses partenaires, Hb et Zelda (Zld), seul ou en combinaison. Mon but était de déterminer comment les divers rapporteurs récapitulent l’expression du promoteur d’hb et d’identifier les rôles spécifiques de chacun de ces facteurs et leurs interactions dans le mécanisme de transcription.De façon intéressante, l’expression du rapporteur avec uniquement neuf sites pour Bcd (trois de plus que dans le gène hb) récapitule l’expression du rapporteur hb-MS2, mais de façon moins rapide et avec un domaine d’expression à la bordure moins nette. Cela suggère qu’en définissant la position de la bordure mais pas sa netteté ni la rapidité de son établissement, Bcd est la source principale d’information positionnelle.En outre, la fixation des partenaires de Bcd au promoteur accélère le processus en agissant à différentes étapes : i) Hb agit en synergie avec Bcd en réduisant les fluctuations du promoteur et en augmentant le taux de démarrage de la polymérase ; ii) Zld abaisse le seuil de concentration de Bcd nécessaire à l’activation par Bcd. En collaboration avec des physiciens, nous avons développé un modèle de transcription impliquant Bcd et fournissant un contexte théorique aux données expérimentales. Ce modèle montre que l’établissement rapide de la bordure d’expression d’hb peut être expliqué par une réaction d’équilibre entre Bcd et ses sites de fixation pour l’information positionnelle nécessitant Zld et Hb pour sa dynamique temporelle.Pour confirmer que Bcd est la seule source d’information positionnelle du système, j’ai comparé la position de la bordure d’expression des gènes rapporteurs dépendant uniquement de Bcd dans des embryons exprimant une ou une demi-dose de Bcd. De manière surprenante, pour chaque rapporteur, le déplacement de la bordure est plus faible que son estimation théorique tenant compte de la constante du gradient exponentiel de concentration de Bcd. Cela indique une constante plus faible pour le gradient d’activité de Bcd et suggère l’existence de sous-populations de Bcd, avec certaines molécules moins actives que d’autres. L’amplitude du déplacement de la bordure du gène rapporteur hb-MS2 est la même que celle obtenue pour les rapporteurs dépendant uniquement de Bcd ce qui confirme que Bcd est bien la seule source d’information positionnelle pour l’expression d’hb Morphogen gradients provide concentration-dependent positional information required to establish the polarity of developmental axes. Although the critical role of these gradients is well recognized, it is unclear how they provide reproducible expression patterns. This is particularly surprising if we consider the stochastic nature of transcription.To address this question, I focus on the establishment of the anterior-posterior (AP) axis of fruit fly embryos, which is mostly defined by Bicoid (Bcd), a very well-characterized morphogen and transcription factor. bcd mRNAs are expressed maternally and anchored at the anterior tip of the oocyte. After egg laying, these mRNAs are translated into proteins, which diffuse through the cytoplasm and form a gradient with its highest concentration at the anterior. A simple model is that depending on their position along the AP axis and thus on Bcd concentration, cells will adopt different fates. However, long debates in the field have questioned the possibility that Bcd-dependent transcription patterns emerge solely from diffusive biochemical interactions between limiting amounts of Bcd molecules and the gene promoter region.The goal of my PhD was to determine how Bcd precisely regulates expression of its main target gene, hunchback (hb). For this, I adapted to synthetic reporters the MS2-MCP system, which allows the fluorescent tagging of mRNAs and provides, thus, a quantitative analysis of transcription dynamics at high spatiotemporal resolution in living embryos. In these reporters, the MS2 sequence was placed under the control of a minimal promoter also containing DNA binding sites for Bcd and/or its known partners, Hb and Zelda (Zld), either alone or in combination. My goal was to determine how the various reporters could recapitulate expression of the hb promoter (hb-MS2 reporter) and shed light on the specific roles of the different factors and their interactions in the transcription mechanism.Interestingly, expression of the reporter with only nine Bcd binding sites (three more than in the hb gene) matches almost perfectly the hb-MS2 reporter pattern, except for the very high steepness of the expression domain boundary and the speed to reach steady-state. This suggests that Bcd alone is the main source of positional information, defining the positioning of the boundary but not its steepness nor the speed of its establishment.In addition, binding of Bcd’s partners to the promoter speed-up the process by acting in different steps of the transcription mechanism: i) Hb synergizes with Bcd by reducing transcription burstiness and increasing the polymerase firing rate; ii) Zld lowers the Bcd concentration threshold required for Bcd-dependent expression. In collaboration with physicists, a biophysical model of Bcd-dependent expression was developed providing a theoretical framework for the experimental data. This model showed that the very rapid establishment of the hb expression boundary can be solely explained by an equilibrium model involving the binding of Bcd molecules to their DNA-binding sites for positional information which requires Zld and Hb for its temporal dynamics.To further confirm that Bcd is the sole source of positional information for hb expression, I compared the boundary position of the Bcd-only dependent reporters in embryos expressing one dose or half dose of Bcd. Surprisingly, the corresponding shifts of these reporters’ boundaries upon one vs half dose of Bcd were smaller than theoretically expected given the measured decay length of the Bcd protein gradient. This indicates a shorter decay length for the Bcd activity gradient and suggests the existence of different Bcd populations, with some Bcd molecules being less active than others. Importantly, the shift observed for the hb-MS2 reporter was the same as for the Bcd-only dependent reporters confirming Bcd as the sole source of positional information for hb expression

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Trotter, Daniel. "Ramifications of Vesicle Release Properties on Information Processing at Central Synapses." Thesis, Université d'Ottawa / University of Ottawa, 2021. http://hdl.handle.net/10393/41628.

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Synapses communicate temporal sequences of action potentials between neurons with variant efficacy, allowing the same axon to convey independent messages to multiple post-synaptic targets. Several molecular mechanisms control information flow in neural networks. In the hippocampus, transmission responses are highly variable even at the level of individual synapses across different cell types and changes dynamically on the multiple time scales on which it operates. Modeling synaptic transmission and dynamics requires balancing the model’s interpretability and its ability to espouse experimental data. In this work, the high variability associated with synaptic responses is first considered at a synapse level. Taking a statistical approach to the phenomena, a biophysically tractable gamma-mixture model is developed to characterize postsynaptic responses from single synapse release events recorded by a sensor for the neurotransmitter glutamate as fluorescence transients. Here the development of this modeling framework leads to three different versions of the framework: two bimodal frameworks that take two different approaches to modeling the noisiness of synaptic releases, and a statistically validated unimodal approach. Variational inference techniques are applied to these frameworks through an expectation-maximization algorithm, which operates on the principles of maximum likelihood. This results in the extraction of latent variables for quantal size, number, and release probability, allowing for the characterization of release events at a synaptic level. A system identification approach is taken to capture the diverse types of synaptic response dynamics observed on short time scales. This extends work from previous phenomenological approaches to account for a nonlinearity and the kinetics evolving on multiple time scales present in this phenomenon. Gradient descent methods are used to estimate synaptic kinetics from complex firing patterns such as those observed \textit{in vivo}. The characterized dynamics in synaptic transmission all contribute to the transfer of information between cells and are assumed to strive for maximizing information transfer through reducing redundancies and optimizing cost-efficiency between the required energy input and the information transferred. The postsynapse has a seeming redundancy as it has two glutamate receptors with different detection thresholds, suggesting there should be a benefit to having both receptors; here this idea is explored here through numerical simulation. Taken together with the modeling of observed glutamate release dynamics, this creates an avenue for improved theory for information processing capabilities of synapses.

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30

Sumner, Christian John. "Spatio-temporal processing in auditory modelling." Thesis, Imperial College London, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.300846.

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Choi, Cecilia. "A biophysically detailed mathematical model of a single late pregnant rat myometrial cell." Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/a-biophysically-detailed-mathematical-model-of-a-single-late-pregnant-rat-myometrial-cell(6d2e1178-370a-4de1-b1fb-9660d1ecf799).html.

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While premature birth is still one of the major clinical problems worldwide, the exact physiological mechanisms underlying myometrium activity during pregnancy remain unclear. In this thesis, a novel biophysically detailed model was constructed using available experimental data to simulate chemical, electrical and mechanical activity in a late pregnant rat uterine myocycte. The developed model has been used to elucidate the ionic mechanism underlying myometrium functionality, providing better insights in the function of the uterus during pregnancy. The model consisted of 15 membrane currents, intracellular calcium handling process coupled with a sliding actin-myosin filament mechanical model to describe uterine behaviour and contractile activity at the single myocyte level. Each of the ionic currents were modelled using Hodgkin-Huxley-type equations. The simulated current traces and current-voltage curves were validated with experimental recordings and the model was further validated by the ability to produce a bursting action potential (AP) during an external stimulus. The model replicated the effects of estradiol during pregnancy, modulating the amplitude and activation properties of individual Ca2+ and K+ currents, therefore altering the AP configuration to a tonic-like plateau. The model also reproduced the actions of drugs to inhibit certain channels to investigate their roles in myometrium. Sensitivity analysis was performed to examine the model's behaviour to changing parameters. A simple 1-D study was conducted to investigate how electrical signals propagate along strand of cells. Although the model successfully replicated results similar to recordings seen in the experiments, limitations have to be addressed and more studies have to be carried out to further improve the model.

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32

Barrass, David Bryan. "Mathematical modelling of pulsatility in neuroendocrine systems." Thesis, Sheffield Hallam University, 1993. http://shura.shu.ac.uk/19321/.

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The work described in this thesis concerns the mathematical description of the characteristic oscillatory electrical behaviour of certain neurosecretory cells found in the hypothalamus of the mammalian brain. This study concentrates on those cells which secrete the hormone oxytocin. A model first described by Hodgkin and Huxley is used as a starting point for the derivation of a description comprising a system of coupled non-linear partial differential equations. The equations have been based wherever possible on experimental data relevant to the system being studied. Where this has not been possible, alternative models based on data from other, related systems have been used. The thesis starts with a discussion of the physiology of the system under study and presents some background material. The second chapter discusses the process of mathematical modelling of neurones and presents some of the relevant work in the area. The model due to Hodgkin and Huxley is significant and is discussed in detail. The research methodology is then outlined. Experimental procedures for recording the electrical behaviour of nerve cells and methods of recording selected ionic currents are the subject of chapter three. Chapter four presents a discussion of oscillatory behaviour in nerve cells at a general level and outlines the features necessary for a nerve cell to exhibit oscillation. The next three chapters discuss the characteristics of the different ionic currents involved and describe the author's derivation of models of these currents. Chapter Five presents the author's model of the sodium current, Chapter Six, the potassium currents and Chapter Seven, the calcium current. The experimental work undertaken and the results obtained are then presented and discussed. During the course of this study a number of computer programs were written and tested by the author. The program listings appear in the appendix. The thesis is significant and contributes to the body of knowledge in that no other mathematical model of the unique bursting behaviour of oxytocin-secreting cells exists as far as the author is aware.

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Li, Tong. "Cross-scale biophysics modelling of F-actin cytoskeleton in cell." Thesis, Queensland University of Technology, 2015. https://eprints.qut.edu.au/82293/1/Tong_Li_Thesis.pdf.

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This thesis is a comparative study of the modelling of mechanical behaviours of F-actin cytoskeleton which is an important structural component in living cells. A new granular model was developed for F-actin cytoskeleton based on the concept of multiscale modelling. This framework overcomes difficulties encountered in physical modelling of cytoskeleton in conventional continuum mechanics modelling, and the computational challenges in all-atom molecular dynamics simulation. The thermostat algorithm was further modified to better predict the thermodynamic properties of F-actin cytoskeleton in modelling. This multiscale modelling framework was applied in explaining the physical mechanisms of cytoskeleton responses to external mechanical loads.

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Adcock, Charlotte. "Molecular modelling and electrostatic properties of ion channels." Thesis, University of Oxford, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.297941.

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35

Gleeson, P. J. "New tools and specification languages for biophysically detailed neuronal network modelling." Thesis, University College London (University of London), 2012. http://discovery.ucl.ac.uk/1347263/.

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Increasingly detailed data are being gathered on the molecular, electrical and anatomical properties of neuronal systems both in vitro and in vivo. These range from the kinetic properties and distribution of ion channels, synaptic plasticity mechanisms, electrical activity in neurons, and detailed anatomical connectivity within neuronal microcircuits from connectomics data. Publications describing these experimental results often set them in the context of higher level network behaviour. Biophysically detailed computational modelling provides a framework for consolidating these data, for quantifying the assumptions about underlying biological mechanisms, and for ensuring consistency in the explanation of the phenomena across scales. Such multiscale biophysically detailed models are not currently in wide- spread use by the experimental neuroscience community however. Reasons for this include the relative inaccessibility of software for creating these models, the range of specialised scripting languages used by the available simulators, and the difficulty in creating and managing large scale network simulations. This thesis describes new solutions to facilitate the creation, simulation, analysis and reuse of biophysically detailed neuronal models. The graphical application neuroConstruct allows detailed cell and network models to be built in 3D, and run on multiple simulation platforms without detailed programming knowledge. NeuroML is a simulator independent language for describing models containing detailed neuronal morphologies, ion channels, synapses, and 3D network connectivity. New solutions have also been developed for creating and analysing network models at much closer to biological scale on high performance computing platforms. A number of detailed neocortical, cerebellar and hippocampal models have been converted for use with these tools. The tools and models I have developed have already started to be used for original scientific research. It is hoped that this work will lead to a more solid foundation for creating, validating, simulating and sharing ever more realistic models of neurons and networks.

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Major, Guy. "The physiology, morphology and modelling of cortical pyramidal neurones." Thesis, University of Oxford, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.306063.

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Wang, Jeffrey Bond. "Modelling Mechanical Interactions Between Cancerous Mammary Acini." Thesis, Harvard University, 2015. http://nrs.harvard.edu/urn-3:HUL.InstRepos:14398530.

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The rules and mechanical forces governing cell motility and interactions with the extracellular matrix of a tissue are often critical for understanding the mechanisms by which breast cancer is able to spread through the breast tissue and eventually metastasize. Ex vivo experimentation has demonstrated the the formation of long collagen fibers through collagen gels between the cancerous mammary acini responsible for milk production, providing a fiber scaffolding along which cancer cells can disorganize. We present a minimal mechanical model that serves as a potential explanation for the formation of these collagen fibers and the resultant motion. Our working hypothesis is that cancerous cells induce this fiber formation by pulling on the gel and taking advantage of the specific mechanical properties of collagen. To model this system, we present a hybrid method where we employ a new Eulerian, fixed grid simulation known as the Reference Map Method to model the collagen as a nonlinear viscoelastic material coupled with a multi-agent model to describe individual cancer cells. We find that these phenomena can be explained two simple ideas: cells pull collagen radially inwards and move towards the tension gradient of the collagen gel, while being exposed to standard adhesive and collision forces. From a computational perspective, we hope that our work can serve as a generalizable framework for future theoretical studies of the mechanical interactions between a large number of cells and a dynamic environment.

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Ghazzawi, Zaid. "Modelling of the craniofacial skeleton : an investigation of skull biomechanics." Thesis, University of Surrey, 2002. http://epubs.surrey.ac.uk/815/.

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Stockley, Edward William. "Three-dimensional reconstruction and electronic modelling of CA1 hippocampal neurones." Thesis, University of Southampton, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295927.

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Tang, Ming. "Atomic-scale biophysics modelling of type I collagen in the extracellular matrix." Thesis, Queensland University of Technology, 2019. https://eprints.qut.edu.au/124650/1/Ming_Tang_Thesis.pdf.

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This thesis explores the biophysics of collagen in the extracellular matrix under external stimuli, by performing cutting edge MD simulations. The obtained results provide significant insights into the design and manufacturing of artificial biomaterials for surgical tissue treatments, of collagen for regenerative medicine applications, and of gold nanoparticles for biomedical applications. The probed biophysical properties consist of the structural properties and the mechanical properties, where the mechanical properties of collagen are regulated by its structure at different levels of hierarchies.

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41

Nordling, Torbjörn E. M. "Issues on modelling of large-scale cellular regulatory networks." Thesis, KTH, Numerical Analysis and Computer Science, NADA, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-4182.

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Vi har identifierat flexibelt utbyte och lagring av data i databaser, tillsammans med långvarig satsning på olika existerande och framtida modeller som nyckar till förståelse av det regler nätverk som utgör bron mellan geno- och fenotyp. Denna pilot studie av modellering av stora cellulära kontroll nätverk utgår från en intressant medicinsk frågeställning inom molekylär cellbiologi: Är framtvingad expression av Cdc6, aktivering av Cdk4/6 och Cdk2 tillräcklig för förankringsfri entré av cell cykelns S fas? Vi försöker konstruera en modell för att besvara denna fråga, på så sätt att vi kan detektera problem vid modellering av stora kontroll nätverk, diskutera implikationer och möjliga lösningar.Vår modell är baserad på 1447 reaktioner och innehåller 1343 olika molekyler. Vi använde graf teori för att studera dess topologi och gjorde följande fynd: Nätverket är skalfritt och avtar enligt en potensfunktion, som var väntat baserat på tidigare arbeten. Nätverket består av ett stort väl förenat kluster. Det kan inte bli modulariserat i form av starka komponenter eller block i en användbar form. Detta eftersom vi fann en stor komponent eller ett stort block som innehöll majoriteten av alla molekyler och mer än hundra små komponenter eller block med en eller några molekyler. Vårt nätverk stämmer inte överens med en hierarkisk nätverks modell bestående av block förenade av cut-vertices. We have identified flexible exchange and storage of data in databases, together with prolonged investment in different existing and future modelling formalisms as key issues in successful understanding of the regulatory network responsible for the connection between geno- and phenotype. This pilot study of modelling of large-scale regulatory networks starts with a medically interesting question from molecular cell biology: Is enforced expression of Cdc6, activation of Cdk4/6 and Cdk2 sufficient for anchorage-independent entry of the S phase of the cell cycle? We try to construct a model for answering this question, in such a way that we can reveal obstacles of large-scale regulatory modelling, discuss their implications and possible solutions.Our model is based on 1447 reactions and contains 1343 different molecules. We used graph theory to study its topology and made the following findings: The network is scale-free and decays as a power-law, as could be expected based on earlier works. The network consists of one huge well connected cluster. It cannot be modularised into strong components or blocks in a useful way, since we get one big component or block containing a majority of all molecules and more than a hundred tiny components or blocks with one or a few molecules. Our network does not agree with a hierarchical network model consisting of blocks linked by cut-vertices.

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42

Qi, Li. "Non-linear finite-element modelling of newborn ear canal and middle ear." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=21904.

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Early hearing screening and diagnosis in newborns are important in order to avoid problems with language acquisition and psychosocial development. Current newborn hearing screening tests cannot effectively distinguish conductive hearing loss from sensorineural hearing loss, which requires different medical approaches. Tympanometry is a fast and accurate hearing test routinely used for the examination of conductive hearing loss for older children and adults; however, the tympanograms are hard to interpret for newborns and infants younger than seven months old due to significant differences in the outer and middle ear. In this work, we used the finite-element method (FEM) to investigate the behaviour of the newborn canal wall and middle ear in response to high static pressures as used in tympanometry. The model results are compared with the analysis results of multi-frequency tympanometry measured in healthy newborns and with available tympanometry measurements in newborns with presumed middle-ear effusion. Analysis results of multi-frequency tympanometry show that both susceptance and conductance increase with frequency. The equivalent volumes calculated from both tails of both the admittance and susceptance functions decreased as frequency increases. The volumes derived from susceptance decrease faster than do those derived from admittance. The 5th-to-95th percentile ranges of equivalent volume and energy reflectances are much lower than previous measurements in older children and adults. Non-linear finite-element models of the newborn ear canal and middle ear were developed. The ear-canal model indicates that the Young's modulus of the canal wall has a significant effect on the ear-canal volume change, which ranges from approximately 27% to 75% over the static-pressure range of ±3 kPa. The middle-ear model indicates that the middle-ear cavity and the Young's modulus of the tympanic membrane (TM) have significant effects on TM volume displacements. The TM volum Il est important d'effectuer un dépistage et un diagnostic précoce de l'audition du nouveau-né afin d'éviter qu'il éprouve plus tard des difficultés dans l'acquisition du langage et dans son développement psychosocial. Les épreuves actuelles de dépistage de l'audition des nouveau-nés ne permettent pas de distinguer efficacement entre une perte auditive due à une surdité de transmission et une perte sensorineurale, chacun de ces troubles exigeant un traitement médical différent. La tympanométrie est une épreuve rapide et exacte que l'on utilise habituellement pour déceler une perte auditive due à une surdité de transmission chez les enfants plus âgés et chez les adultes. Cependant, dans le cas des nouveau-nés et des enfants en bas âge, les tympanogrammes sont difficiles à interpréter en raison de différences importantes dans l'oreille moyenne et externe. Dans cette étude, nous avons utilisé l'analyse par éléments finis pour examiner les comportements que manifestent la paroi du conduit auditif et l'oreille moyenne des nouveau-nés en réaction aux pressions statiques élevées utilisées en tympanométrie. Les résultats du modèle sont ensuite comparés aux résultats d'analyses de tympanométrie multifréquence effectuées sur des nouveau-nés en santé, et aux mesures tympanométriques disponibles réalisées sur des nouveau-nés souffrant d'un épanchement présumé dans l'oreille moyenne. Les résultats d'analyses de tympanométrie multifréquence indiquent que tant la susceptance que la conductance augmentent avec la fréquence. Les volumes équivalents calculés à partir de deux extrémités des fonctions d'admittance et de susceptance décroissent à mesure que la fréquence augmente. Les volumes issus de la susceptance diminuent plus rapidement que ceux issus de l'admittance. Les réflectances d'énergie et les volumes équivalents comprises dans une plage allant du 5e au 95e percentile sont beaucoup moins élevées que les$

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Li, Chen. "Biophysically detailed modelling of the pro-arrhythmic effects of heart failure-induced ionic remodelling." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/biophysically-detailed-modelling-of-the-proarrhythmic-effects-of-heart-failureinduced-ionic-remodelling(b761b2b9-5bea-4d38-82b0-aa3c74eab967).html.

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Heart Failure is a common long term progressive and serious medical condition with high mortality and costly health services in the UK. By the year of 2010, there were around 90,000 people in the UK suffered from heart failure and in 2008, 10,000 heart failure patients were recorded death. Treatments of heart failure cost the National Health Service around £625 million every year. Although heart failure is highly pro-arrhythmic, the underlying mechanisms of the pro-arrhythmic effects of heart failure are not completely understood. Heart failure is associated with electrical remodelling of the properties and kinetics of some ionic channels responsible for the action potential of cardiac cells. However, it is still unclear whether this ionic channel remodelling can account for the pro-arrhythmic effects of heart failure as the complexity of the heart impedes a detailed experimental analysis. Biophysically detailed computational models have been developed in the last two decades, enabling the evaluation of experimental data. The aim of this thesis is to use arrhythmic mechanisms to investigate the pro-arrhythmic effects of heart failure-induced remodelling on the cardiac action potentials and Purkinje-ventricular junction. Single canine Purkinje fibre and ventricular cell models were developed to investigate the effects of heart failure-remodelled ionic channel currents on cell action potentials and identify optimal options for the potential clinical treatments. One-dimensional strand tissue model and three-dimensional wedge model were developed to further explore the effects of heart failure-induced remodelling in propagation of the canine Purkinje fibre, ventricle and Purkinje-ventricular junction. It was found that heart failure-induced remodelling on the Purkinje fibre and ventricle reduced the conduction safety and increased tissue’s vulnerability to the genesis of the unidirectional conduction block, especially at the Purkinje-ventricular junction, which may cause conduction failure, re-entry or both.

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Ouldridge, Thomas E. "Coarse-grained modelling of DNA and DNA self-assembly." Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:b2415bb2-7975-4f59-b5e2-8c022b4a3719.

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In this thesis I present a novel coarse-grained model of deoxyribonucleic acid (DNA). The model represents single-stranded DNA as a chain of rigid nucleotides, and includes potentials to represent chain connectivity, excluded volume, hydrogen-bonding and base stacking interactions. The parameterization of these interactions is justified by comparing the model's representation of a range of physical phenomena to experimental data. In particular, the geometrical structure and elastic moduli of duplex DNA, and the flexibility of single-stranded DNA, are shown to be physically reasonable. Additionally, the thermodynamics of single-stranded stacking, duplex hybridization, hairpin formation and more complex motifs are shown to agree well with experimental data. The model is optimized for capturing the thermodynamic and mechanical changes associated with duplex formation from single strands. Considerable attention is therefore given to ensuring that single-stranded DNA behaves physically, an approach which differs from previous attempts to model DNA. As a result, the model is the first in which an explicit stacking transition is present in single strands, and also the only coarse-grained model to date to capture both hairpin formation within a single strand and duplex formation between strands. The scope of the model is demonstrated by simulating DNA tweezers, an iconic nanodevice -- the first time that coarse-grained modelling has been applied to dynamic DNA nanotechnology. The simulations suggest that branch migration during toehold-mediated strand displacement -- a central feature of many nanomachines -- does not have a flat free-energy profile, as is generally assumed. This finding may help to explain the observed dependence of displacement rate on toehold length. Finally, the operation of a two-footed DNA walker on a single-stranded DNA track is considered. The model suggests that several aspects of the walker will reduce its efficiency, including a tendency to bind to an undesired site on the track. Several design modifications are suggested to improve the operation of the walker.

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45

Maksym, Geoffrey N. "Modelling lung tissue theology." Thesis, McGill University, 1997. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=42087.

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A model was developed to account for the static elastic behaviour of the lung tissue strip in terms of distributions of collagen and elastin fibers. Distributions of collagen fiber lengths and elastin fiber stiffnesses were determined by fitting the model to data from dog lung tissue strips. These distributions followed 1/f power-laws for more than 95% of the data. Computer simulations of two dimensional tissue strip models with 1/f distributions of collagen fiber lengths also predicted realistic stress-strain curves. The simulations illustrated the gradual development of geometric and stress heterogeneity throughout the tissue as the collagen fibers were recruited during stretch. This model suggests a mechanistic basis for the shape of the pressure-volume curve of whole lung. It also indicates how this curve may be affected by changes in tissue collagen and elastin similar to the changes occurring in the diseases of pulmonary emphysema and fibrosis. Nonparametric block-structured nonlinear models for describing both the static and dynamic stress-strain behaviour of the lung were applied to dog lung tissue strips and to whole rat lungs in vivo. Both the Wiener and Hammerstein models accounted for more than 99% of the tissue strip data, although the Hammerstein model was more consistently accurate across a range of perturbation amplitudes and operating stresses. Plastic dissipation of energy within the lung tissue strip was estimated at less than 20% of the total dissipation during slow sinusoidal cycling. The Hammerstein model was also the best of those investigated for describing the rat lung data in vivo, although there were dependencies of the model parameters on perturbation amplitude and operating point that indicate that a more complicated model is required for the whole lung. Finally, construction of a fiber recruitment model for the dynamic mechanical behaviour of lung tissue strips was attempted. However accurate reproduction of measured behaviour was no

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Khanal, Bishesh. "Modélisation et simulation réaliste d'IRMs cérébrales structurelles longitudinales avec atrophie appliquées à la maladie d'Alzheimer." Thesis, Nice, 2016. http://www.theses.fr/2016NICE4046/document.

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Dans cette thèse, nous avons développé des outils pour simuler des imageslongitudinales réalistes de cerveau présentant de l’atrophie ou de lacroissance. Cette méthode a été spécifiquement élaborée pour simuler leseffets de la maladie d’Alzheimer sur le cerveau. Elle se fonde sur un modèle dedéformation du cerveau qui décrit les effets biomécaniques d’une perte detissue due à une carte d’atrophie prescrite. Nous avons élaboré une méthodepour interpoler et extrapoler les images longitudinales d’un patient en simulantdes images avec une carte d’atrophie spécifique au sujet. Cette méthode a étéutilisée pour interpoler des acquisitions temporelles d’Images par RésonnanceMagnétique (IRM) de 46 patients souffrant de la maladie d’Alzheimer. Pour cefaire, des cartes d’atrophie sont estimées pour chaque patient, d’après deuxacquisitions IRM temporelles distinctes. Les IRM cliniques présentent du bruitet des artefacts. De plus, les acquisitions longitudinales présentent desvariations d’intensité d’une image à l’autre. Nous avons donc élaboré uneméthode qui combine le modèle de déformation du cerveau, ainsi que lesdifférentes images cliniques disponibles d’un patient donné, afin de simuler lesvariations d’intensité des acquisitions longitudinale. Pour finir, les outils desimulation d’images réalistes développés au cours de cette thèse sont mis àdisposition en open-source This thesis develops a framework to simulate realistic longitudinal brainimages with atrophy (and potentially growth), particularly in the case ofAlzheimer's Disease (AD). The core component of the framework is a braindeformation model: a carefully designed biomechanics-based tissue loss modelto simulate the deformations having the prescribed atrophy. The thesispresents a method to interpolate or extrapolate longitudinal images of asubject by simulating images with subject-specific atrophy patterns. Themethod was used to simulate interpolated time-point Magnetic ResonanceImages (MRIs) of 46 AD patients by prescribing atrophy estimated for eachpatient from the available two time-point MRIs. Real MRIs have noise andimage acquisition artefacts, and real longitudinal images have variation ofintensity characteristics among the individual images. In this thesis, wepresent a method that uses our brain deformation model and different availableimages of a subject to add realistic variations of intensities in the syntheticlongitudinal images. Finally, the software developed during the thesis tosimulate realistic longitudinal brain images with our brain deformation modelis released open-source

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Sulc, Petr. "Coarse-grained modelling of nucleic acids." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:3e1573ec-033c-4971-85e1-ccecd57e7f70.

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This thesis considers coarse-grained models of DNA and RNA, developed in particular to study nanotechnological applications as well as some important biophysical processes. We first introduce sequence-dependent thermodynamics into a previously developed coarse-grained rigid base-pair model of DNA. This model is then used to study sequence-dependent effects in multiple DNA systems including: the heterogeneous stacking transition of single strands, the fraying of a duplex, the effects of stacking strength in the loop on the melting temperature of hairpins, the force-extension curve of single strands, and the structure of a kissing-loop complex. We further apply the DNA model to study in detail the properties of an autonomous unidirectionally propagating DNA nanotechnological device, called the ``burnt bridges motor''. We then apply the coarse-graining methods developed for the DNA model to construct a new sequence-dependent coarse-grained model of RNA, which aims to capture basic thermodynamic, structural and mechanical properties of RNA molecules. We test the model by studying its thermodynamics for a variety of secondary structure motifs and also consider the force-extension properties of an RNA duplex. This RNA model allows for efficient simulations of a variety of RNA systems up to hundreds or even thousands of base-pairs. Its versatility is further demonstrated by studying the thermodynamics of a pseudoknot folding, the formation of a kissing loop complex, the structure of a hexagonal RNA nanoring, and the unzipping of a hairpin.

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Ainsley, Jon. "Computational simulations of enzyme dynamics and the modelling of their reaction mechanisms." Thesis, Northumbria University, 2017. http://nrl.northumbria.ac.uk/36286/.

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Proteins and enzymes are large and complex biological molecules, characterized by unique three-dimensional structure are highly flexible and dynamic nature. Thorough understanding of protein and enzyme function requires studying of their conformational flexibility, because important physiological processes, such as ligand binding and catalysis rely on an enzyme’s dynamic nature and their ability to adopt a variety of conformational states. Computational methods are widely applied in studying enzymes and proteins structure and function providing a detailed atomistic-level of resolution data about the dynamics and catalytic processes, mechanisms in biomolecules, therefore even more nowadays a term ‘computational enzymology’ has emerged. Experimental methods often have difficulty in predicting dynamic motions of proteins. Computational simulations techniques, such as Molecular Dynamics simulations, have proven successful in simulating the conformational flexibility of proteins in studying structure-function relationships. Additionally, the binding events between two molecules, e.g. an enzyme and its substrate, can be computationally predicted with molecular docking methods. Enzymes are proteins that catalyse almost all biochemical reactions and metabolic processes in all organisms. In order to study the conformational flexibility of proteins we apply molecular dynamics simulations, and in order to simulate their reaction mechanisms we apply quantum mechanical simulations. Quantum mechanical simulations can also be used to predict the electronic structure of organic compounds, by calculating their electronic structures we perform orbital analyses and predict their optical properties. The results gained from our computational simulations can give new insights into explanation of experimental findings and data and can inspire and guide further experiments.

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Adeniran, Ismail. "Biophysically detailed modelling of the functional impact of gene mutations associated with the 'short QT syndrome'." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/biophysically-detailed-modelling-of-the-functional-impact-of-gene-mutations-associated-with-the-short-qt-syndrome(f602c1f4-4290-469e-a66a-878198b17c7d).html.

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The recently identified genetic short QT syndrome is characterised by abbreviated QT intervals on the electrocardiogram, an increased risk of atrial and ventricular arrhythmias, and an increased risk of sudden death. Although the short QT syndrome has been suggested to provide a paradigm for increasing understanding of the role of potassium channels in ventricular fibrillation, the basis for arrhythmogenesis in the short QT syndrome is incompletely understood. There are no animal models that accurately reproduce a short QT phenotype, and whilst in vitro electrophysiology of short QT mutant channels provides a route to greater understanding of the effects of short QT mutants on action potential repolarisation, on its own, this approach is insufficient to explain how arrhythmias arise and are maintained at the tissue level. Consequently, this thesis is concerned with the use of the viable alternative; in silico (computational) modelling to elucidate how the short QT syndrome facilitates the genesis and maintenance of ventricular arrhythmias and its effects on ventricular contraction. Using extant biophysical data on changes induced by the short QT mutations and data from BHF-funded in vitro electrophysiology, three novel mathematical models of the first three variants of the short QT syndrome were developed; a Markov chain model for short QT variant 1, a Markov chain model for short QT variant 2 and a Hodgkin-Huxley model for short QT variant 3. These models were incorporated into single cell and anatomically detailed tissue and organ computer models to elucidate how these variants lead to ventricular arrhythmias. The developed short QT models were then incorporated into electromechanically coupled single cell and tissue models to investigate the effects of the short QT mutants on ventricular contraction. It was found that each short QT variant uniquely increased the transmural dispersion of action potential duration across the ventricular wall, increased the temporal window of tissue vulnerability to premature excitation stimulus, leading to increased susceptibility to re-entrant arrhythmia.

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Thompson, Neill Stuart. "Musculoskeletal modelling in the assessment of lower limb biomechanical pathology in cerebral palsy children and the effects of interventions to improve their gait." Thesis, Queen's University Belfast, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.301748.

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Dissertations / Theses on the topic 'Biophysical modelling'

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